CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kivinen, L.
Right arrow Articles by Laiho, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kivinen, L.
Right arrow Articles by Laiho, M.
Cell Growth & Differentiation Vol. 10, 621-628, September 1999
© 1999 American Association for Cancer Research

Ras- and Mitogen-activated Protein Kinase Kinase-dependent and -independent Pathways in p21Cip1/Waf1 Induction by Fibroblast Growth Factor-2, Platelet-derived Growth Factor, and Transforming Growth Factor-ß11

Laura Kivinen and Marikki Laiho2

Haartman Institute, Department of Virology, University of Helsinki, FIN-00014 Helsinki, Finland

p21Waf1/Cip1 (hereafter referred to as p21) is up-regulated in differentiating and DNA-damaged cells, but it is also up-regulated by serum and growth factors. We show here that fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), and transforming growth factor-ß1 (TGF-ß1) all induce p21 expression in mouse fibroblasts, but with markedly different kinetics. We link their effect on p21 to Ras and mitogen-activated protein kinase kinase-1(/2) [MEK1(/2)]-regulated pathways using either a specific MEK1(/2) inhibitor (PD 098059) or cells expressing conditionally activated Ras or dominant negative Ras. We demonstrate that p21 induction by PDGF and TGF-ß1 requires MEK1(/2) and, additionally, that the TGF-ß1 effect on p21 depends on Ras, whereas the PDGF effect does not. In contrast, FGF-2 regulation of p21 is largely independent of MEK and Ras. However, PD 098059 efficiently inhibited S-phase entry of quiescent cells induced by either FGF-2 or PDGF, suggesting separate signaling pathways for FGF-2 in induction of p21 and in S-phase entry. The results suggest different but partly overlapping signaling pathways in growth factor regulation of p21.




This article has been cited by other articles:


Home page
Circ. Res.Home page
F. S. Santiago, H. Ishii, S. Shafi, R. Khurana, P. Kanellakis, R. Bhindi, M. J. Ramirez, A. Bobik, J. F. Martin, C. N. Chesterman, et al.
Yin Yang-1 Inhibits Vascular Smooth Muscle Cell Growth and Intimal Thickening by Repressing p21WAF1/Cip1 Transcription and p21WAF1/Cip1-Cdk4-Cyclin D1 Assembly
Circ. Res., July 20, 2007; 101(2): 146 - 155.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. Tu, W. Wu, T. Wu, Z. Cao, R. Wilkins, B.-H. Toh, M. E. Cooper, and Z. Chai
Antiproliferative Autoantigen CDA1 Transcriptionally Up-regulates p21Waf1/Cip1 by Activating p53 and MEK/ERK1/2 MAPK Pathways
J. Biol. Chem., April 20, 2007; 282(16): 11722 - 11731.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
L. Bockstaele, H. Kooken, F. Libert, S. Paternot, J. E. Dumont, Y. de Launoit, P. P. Roger, and K. Coulonval
Regulated Activating Thr172 Phosphorylation of Cyclin-Dependent Kinase 4(CDK4): Its Relationship with Cyclins and CDK "Inhibitors"
Mol. Cell. Biol., July 1, 2006; 26(13): 5070 - 5085.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
A. Moustakas and C.-H. Heldin
Non-Smad TGF-{beta} signals
J. Cell Sci., August 15, 2005; 118(16): 3573 - 3584.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
N. Gao, D. C. Flynn, Z. Zhang, X.-S. Zhong, V. Walker, K. J. Liu, X. Shi, and B.-H. Jiang
G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells
Am J Physiol Cell Physiol, July 6, 2004; 287(2): C281 - C291.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Yu, X.-W. Liu, and H.-R. C. Kim
Platelet-derived Growth Factor (PDGF) Receptor-{alpha}-activated c-Jun NH2-terminal Kinase-1 Is Critical for PDGF-induced p21WAF1/CIP1 Promoter Activity Independent of p53
J. Biol. Chem., December 5, 2003; 278(49): 49582 - 49588.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Dupont, M. Karas, and D. LeRoith
The Cyclin-dependent Kinase Inhibitor p21CIP/WAF Is a Positive Regulator of Insulin-like Growth Factor I-induced Cell Proliferation in MCF-7 Human Breast Cancer Cells
J. Biol. Chem., September 26, 2003; 278(39): 37256 - 37264.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
S.-M. Kakonen, K. S. Selander, J. M. Chirgwin, J. J. Yin, S. Burns, W. A. Rankin, B. G. Grubbs, M. Dallas, Y. Cui, and T. A. Guise
Transforming Growth Factor-{beta} Stimulates Parathyroid Hormone-related Protein and Osteolytic Metastases via Smad and Mitogen-activated Protein Kinase Signaling Pathways
J. Biol. Chem., July 5, 2002; 277(27): 24571 - 24578.
[Abstract] [Full Text] [PDF]


Home page
Sci SignalHome page
N. Olashaw and W. J. Pledger
Paradigms of Growth Control: Relation to Cdk Activation
Sci. Signal., May 28, 2002; 2002(134): re7 - re7.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. K. Jackson, A. DeLoose, and K. M. Gilbert
Induction of Anergy in Th1 Cells Associated with Increased Levels of Cyclin-Dependent Kinase Inhibitors p21Cip1 and p27
J. Immunol., January 15, 2001; 166(2): 952 - 958.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Yue and K. M. Mulder
Requirement of Ras/MAPK Pathway Activation by Transforming Growth Factor {beta} for Transforming Growth Factor {beta}1Production in a Smad-dependent Pathway
J. Biol. Chem., October 6, 2000; 275(40): 30765 - 30773.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
K. Pardali, A. Kurisaki, A. Moren, P. ten Dijke, D. Kardassis, and A. Moustakas
Role of Smad Proteins and Transcription Factor Sp1 in p21Waf1/Cip1 Regulation by Transforming Growth Factor-{beta}
J. Biol. Chem., September 22, 2000; 275(38): 29244 - 29256.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Yue and K. M. Mulder
Requirement of Ras/MAPK Pathway Activation by Transforming Growth Factor {beta} for Transforming Growth Factor {beta}1Production in a Smad-dependent Pathway
J. Biol. Chem., October 6, 2000; 275(40): 30765 - 30773.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
K. Pardali, A. Kurisaki, A. Moren, P. ten Dijke, D. Kardassis, and A. Moustakas
Role of Smad Proteins and Transcription Factor Sp1 in p21Waf1/Cip1 Regulation by Transforming Growth Factor-{beta}
J. Biol. Chem., September 22, 2000; 275(38): 29244 - 29256.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.